Altosid® IGR: Product Information

Product Information - Technical Information

Chemical Characteristics

(S)-Methoprene belongs to the terpenoid class of compounds, as do natural products, such as essential oils and other plant-produced materials.

Chemical Name:	Isopropyl (2E,4E,7S)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate
Technical Name:	(S)-Methoprene
CAS Number:	65733-16-6
Empirical Formula:	C₁₉H₃₄O₃
Properties:	Amber liquid Slight fruity odor Soluble in organic solvents

Environmental Fate

Persistence and Movement in Soil: The half-life of (S)-Methoprene under aerobic conditions in sandy loam is approximately ten days when applied at the exaggerated rate of 1000 g/Ha. Most of the applied dose is converted rapidly to CO₂. (S)-Methoprene remains bound in the top few centimeters of the soil even after repeated washings with water. Thus, it should not persist, leach or contaminate ground water.

Fate in Plants: When applied at the rate of 1000 g/Ha on alfalfa,
(S)–Methoprene has a half-life of less than two days and less than one day on rice. It is metabolized rapidly, yielding products that are further degraded to normal plant nutrients.

Fate in the Food Chain: In a model ecosystem study, it was shown that (S)-Methoprene does not accumulate in the food chain. It was demonstrated that biodegradation and lack of persistence characterize (S)-Methoprene in the environment.

Persistence in Water: In the field, (S)-Methoprene has a half-life of 30-45 hours in unsterilized pond water. If the water is exposed to sunlight, the half-life is significantly reduced.

Safety Studies

An extensive toxicological database has been generated to support EPA registrations of products containing (S)-Methoprene. (S)-Methoprene products exhibit a wide margin of safety and no acute handling hazard by any exposure route.

Development/Reproductive Toxicity

Teratogenicity
(S)-Methoprene is not a teratogenic compound.

The NOEL for maternal and embryotoxicity in rabbits was 200 mg/kg/day. The NOEL for reproductive effects in rats was 500 ppm.

Mutagenicity
(S)-Methoprene is not a mutagenic compound.

Acute, Subchronic and Chronic Toxicity of (S)-Methoprene in Animals:

Species	Study Type	Result
Rat	Oral LD₅₀	> 34,600*
Dog	Oral LD₅₀	> 5,000*
Rabbit	Dermal LD₅₀	> 3,000*
Rat	Inhalation LD₅₀	> 210 mg/l air
Dog	Inhalation LD₅₀	No effect at 20-30 mg/kg*
Rabbit	Dermal irritation	Non-irritating
Rabbit	Ocular irritation	Non-irritating
Rat	90-day feeding	NOEL = 1,000 ppm
Dog	90-day feeding	NOEL = 500 ppm
Rabbit	30-day dermal	NOEL = 0.1 ml/kg/day
Rat	21-day inhalation	NOEL > 20 mg/l (2,000 ppm)
Dog	28-day inhalation	NOEL > 0.0625 mg/kg/day
Rat	Chronic feeding (2-year)	NOEL > 5,000 ppm
Mouse	Chronic feeding (2-year)	NOEL > 2,500 ppm
*Highest dose tested

Metabolism in Cattle

Extensive laboratory and field experiments have shown that (S)-Methoprene is rapidly degraded by mammalian metabolic systems and readily converted to natural body constituents. When steers or cows are treated orally with (S)-Methoprene, the compound is excreted either unchanged or metabolized quickly and eliminated via urine, feces and expired breath. Chemical identification of (S)-Methoprene degradation products in milk and blood one week after the oral administration of radio labeled (S)-Methoprene to a cow revealed that it was metabolized to simple acetates that are mostly incorporated into fatty acids, lactose and cholesterol. (S)-Methoprene metabolites were not detected in tissues. In a cow and growing steer, unmetabolized (S)-Methoprene was mainly excreted through feces, whereas up to 19.8% of the orally administered dose was excreted in urine as radioactive metabolite. The highest radioactivity was in bile, and the next highest was in the liver. All muscles of the cow had < 0.1 ug of the total radioactivity per gram.

Effects on Beneficial Insects

Residual insecticides, such as organophosphates, are toxic to beneficial insects, such as coprophagous flies and beetles, predaceous beetles, parasitic wasps and dung beetles. Altosid^® IGR does not disrupt dung composition and does not harm beneficial insects.

Effects on Horses

Horses (1/dose group) have been experimentally dosed with
(S)–Methoprene, as follows, without adverse clinical signs or loss of appetite. Accidental exposure to (S)-Methoprene via cattle feed would not be anticipated to pose any toxicological risk.

Dose*	Route	Timeframe
1 and 3 mg AI/kg	Oral feed supplement	14 days
6 and 12 mg AI/kg	1 gal. H₂O via stomach tube	1 day
6 mg AI/kg	Oral feed supplement	7 days
12 mg AI/kg	Oral feed supplement	7 days
*Active ingredient given per body weight of animal per dose

Regulatory Status of (S)-Methoprene

(S)-Methoprene is an insect growth regulator (IGR) with activity against fleas, mosquitoes, horn flies, ants, sciarid flies and stored product pests.

The active ingredient, (S)-Methoprene, was first registered by the EPA in 1975. (S)-Methoprene was classified as the first biochemical pesticide and therefore is currently regulated by the Biopesticide Division of the EPA.

(S)-Methoprene has completed an extensive reregistration process, resulting in the publication by the EPA of the Reregistration Eligibility Document (RED) in 1991.

In June 2003, the Environmental Protection Agency (EPA) announced that (S)-Methoprene is exempt from the requirement of a tolerance in or on all food commodities when used to control insect larvae. The EPA granted the exemption because a thorough risk analysis showed residue tolerances are not necessary to protect human health or the environment.

After discussions between the EPA and FDA, it was decided that feed-through uses of (S)-Methoprene in cattle feed to control horn flies should be regulated by the EPA. Altosid^® IGR Feed-Thru was the first (S)-Methoprene cattle product registered by the EPA in 1975.

Regulatory Status of Altosid^® IGR Feed-Thru

The following excerpt from the 2005 Feed Additive Compendium summarizes the regulatory status of the use of (S)-Methoprene in cattle feed.

FDA Status: No feed mill license required. Product is a food additive. 40 CFR 180.1033 (EPA) (S)-Methoprene is exempted from the requirement of a tolerance in or on all food commodities when used to control insect larvae. When used in medicated feeds, medicated feed application requirement is determined by regulatory status of the drug.

EPA Status: Product is a pesticide when used in non-medicated feeds. EPA registration is required for feeds offered for sale except when custom blended per the provisions of 40 CFR 167.3. In medicated feeds, the product is a food additive and no EPA registration is required when the source of (S)–Methoprene is an EPA-registered product.

Feed Additives That Control Immature Horn Flies in Cattle Manure

Trade Name	Altosid^® IGR Feed-Thru	Rabon™ Oral Larvicide
Manufacturer	Wellmark International	KMG Chemicals, Inc.
Active Ingredient	(S)-Methoprene	Tetrachlorvinphos
% Active in Concentrate	0.4, 1.0, 2.0, 10.5	7.76, 97.3
Classification	Terpenoid ester	Organophosphate insecticide
Mode of Action	Insect Growth Regulator	Cholinesterase inhibitor
Activity	Kills larvae	Kills larvae
Product Forms	Dry powder, meal, liquid micro-emulsion	Granulated material, meal
Administration	Mineral, block, tub, top-dress, liquid feed	Mineral, block, tub, top-dress, liquid feed
Dosage	0.8–1.5 mg active/100 lbs. of body weight	70 mg of active/100 lbs. of body weight
Cattle Age Restrictions	None	None